Psychological and methodological issues in substance abuse treatment/research are under investigation as part of the clinical trials evaluating cocaine and opioid abuse treatments. One area of focus is improving methods of monitoring cocaine use to increase the ability of clinical trials to detect effective treatments. Quantitative urinalysis and newly developed criteria for identifying new cocaine use were evaluated as alternative measures of cocaine use. Urine specimens collected in a cocaine dosing study in non-treatment- seeking subjects and a cocaine treatment trial were analyzed for the cocaine metabolite, benzoylecgonine, with qualitative and quantitative methods. Pharmacokinetic criteria ("New Use" rules) were applied to quantitative data to identify occasions of new cocaine use. Results were compared to known cocaine administrations in the laboratory study and to self-reported drug use and qualitative urinalysis for subjects in the clinical trial. New Use criteria correctly identified cocaine administrations in the cocaine dosing study in all but a small number of specimens. In the clinical trial, quantitative urinalysis and estimated New Uses provided more information about patterns and frequency of use than qualitative urinalysis in the different treatment conditions in the clinical trial. Interpretation of quantitative urinalysis with New Use rules appears to be a useful method for monitoring treatment outcome and may be more accurate than traditional qualitative urinalysis in estimating frequency of cocaine use. This procedure is being adopted as an outcome measure in clinical trials around the country. Other methods of monitoring drug use are also being evaluated. These methods include sweat patches and quantitative urinalysis of cocaine. A second area of focus is on the impact of family history on drug use. Results to date suggest that opioid- dependent patients with comorbid mental disorder were over twice as likely to have a parent with substance dependence disorders and over three times more likely to have any sibling with substance dependence as were opioid dependent patients without a comorbid mental disorder. These results suggest a relationship between psychiatric comorbidity and familial influence of substance dependence. Additional research is underway to evaluate methods for measuring craving and predictors of treatment outcome.